Genetics On the Forefront of New Cystic Fibrosis Treatment

Up until recently, most treatment methods for CF have focused on supportive treatments, clearing airway secretions, and maintaining nutritional status. Luckily, as we begin to learn more about the genetics of certain diseases such as CF, they offer a potential new way forward for targeted treatment. The first leap in this precision medicine began in 2012 with the licensing of a small molecule called ivacaftor, that targets the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene has been well established as the mutation site that is what results in CF. There are many types of mutations to the CFTR gene that can occur and cause CF. In one sense this can make it challenging to develop drugs that help patients, while on the other hand it provides an even greater opportunity for individualizing treatment. Ivacaftor has been shown to be successful in improving CFTR function in patients, and more molecular drugs are being looked at to target CFTR gene mutations. 

Targeted therapies offer the promise of not only an increase in effective treatment options for people with CF, but also more individualized care. The concept and benefit of targeted genetic therapies has been recognized in oncology for some time. With targeted genetic therapies, molecular biomarkers can be used for individuals or groups of individuals to develop effective and highly precise individualized treatments. This differs from most drugs currently on the market that are designed to target broad groups of people with a certain disease.

Ivacaftor is a CFTR gene potentiator, meaning that it increases the activity of this gene. In people with certain CFTR gene mutations, this is what they need. In 2015 another drug called lumacaftor also received FDA approval for CF treatment. Lumacaftor is called a corrector and has been approved for combination use with ivacaftor for people with the most common CFTR mutations. While many mutations outside of the CFTR gene have been shown to exist in people with CF, a small number of mutations seems to be primarily responsible for the majority of CF cases.

There is no denying that the relationship between genetics and symptoms of CF is complex. On a basic level, patients who have lower levels of sweat chloride (caused by CFTR mutations) generally have longer lifespans, less symptoms, and better lung function than people with higher levels. Thus, targeting the CFTR gene as a focus for treatment holds immense promise in increasing survivability and decreasing symptoms in people with CF.

What types of therapeutics are being looked at now?

Gene therapy is one potential treatment option for CF patients that has been under review. Gene therapy is “an experimental technique that that uses genes to treat or prevent disease.” With CF researchers are looking at introducing non-mutated CFTR genes into the epithelial cells of patients in the hopes that this will enable them to express the gene properly, which will ideally lessen their symptoms.

Read on to learn more about how genetics has helped revolutionize cystic fibrosis treatment.